Molecular pharmacological aspects of histamine receptors

Leurs, Rob; Smit, Martine J.; Timmerman, H.

doi:10.1016/0163-7258(95)00006-3

Cited by 332 publications

(286 citation statements)

References 275 publications

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“…The immediate effects of histamine H3 antagonists on methamphetamine-induced dopamine release could be due in part to the increased intracellular availability of Ca 2 þ they produce, since activation of histamine H3 receptors has been suggested to inhibit the influx of Ca 2 þ (eg Endou et al, 1994;Leurs et al, 1995). Increased availability of Ca 2 þ may directly facilitate the release of dopamine and/or other neuromodulators that may indirectly enhance dopamine transmission.…”

Section: Discussionmentioning

confidence: 99%

Histamine H3 Receptor Antagonists Potentiate Methamphetamine Self-Administration and Methamphetamine-Induced Accumbal Dopamine Release

Munzar

Justinová²,

Goldberg³

2004

Neuropsychopharmacol

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Methamphetamine administration increases brain levels of histamine and neuronal histamine attenuates several of methamphetamine's behavioral effects. The role of different subtypes of histamine receptors in this negative feedback, however, remains unclear. There is some evidence on possible involvement of histamine H3 receptors in these actions of methamphetamine. The aim of the present study was to evaluate the effects of two histamine H3 receptor antagonists, clobenpropit and thioperamide, on rewarding and neurochemical effects of methamphetamine utilizing three in vivo methodologies, drug self-administration, drug discrimination, and microdialysis in Sprague-Dawley rats. In rats self-administering methamphetamine intravenously under a fixed-ratio schedule, presession treatment with thioperamide (1.0-3.0 mg/kg, subcutaneous, s.c.) or clobenpropit (1.0-3.0 mg/kg, s.c.) potentiated the reinforcing effects of methamphetamine, as indicated by a dose-dependent increase in responding for a low 0.03 mg/kg dose of methamphetamine, that by itself failed to maintain responding above saline substitution levels, and a decrease in responding for a higher 0.06 mg/kg training dose of methamphetamine. In contrast, neither thioperamide nor clobenpropit treatment increased responding during saline substitution. In other rats trained to discriminate intraperitoneal (i.p.) injection of 1.0 mg/kg methamphetamine from i.p. injection of saline, both thioperamide and clobenpropit (0.3-3.0 mg/kg, s.c.) dose dependently increased methamphetamine-appropriate responding when administered with a low 0.3 mg/kg i.p. dose of methamphetamine, which by itself produced predominantly saline-appropriate responding. However, thioperamide and clobenpropit produced only saline-appropriate responding when administered with saline vehicle. Finally, thioperamide and clobenpropit potentiated methamphetamine-induced elevations in extracellular dopamine levels in the shell of the nucleus accumbens, but did not increase brain dopamine levels when given alone. These findings point to histamine H3 receptors as a new and important receptor system modulating the reinforcing, subjective, and neurochemical actions of methamphetamine.

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Section: Discussionmentioning

confidence: 99%

Histamine H3 Receptor Antagonists Potentiate Methamphetamine Self-Administration and Methamphetamine-Induced Accumbal Dopamine Release

Munzar

Justinová²,

Goldberg³

2004

Neuropsychopharmacol

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“…Histamine induces a Ca 21 signal in human macrophages by activating the H 1 receptor, which is coupled with the phospholipase C-pathway [41,42]. To evaluate whether NCX can operate in the forward mode contributing to restore Ca 21 gradients after a receptor-mediated Ca 21 -spike event, we preincubated HLM Effects of Na 1 -free medium on exocytosis and cytokine/chemokine production in HLM Macrophages and monocytes rely on Ca 21 signaling to activate cell functions relevant to inflammation and immune regulation.…”

Section: Effect Of Cb-dmb On the [Ca 21 ] I Increase Induced By Histamentioning

confidence: 99%

“…Histamine induces a Ca 21 signal in human macrophages by activating the H 1 receptor, which is coupled with the phospholipase C-pathway [41,42]. To evaluate whether NCX can operate in the forward mode contributing to restore Ca 21 gradients after a receptor-mediated Ca 21 -spike event, we preincubated HLM with CB-DMB before stimulation with histamine (1 mM).…”

Section: Effect Of Cb-dmb On the [Ca 21 ] I Increase Induced By Histamentioning

confidence: 99%

Expression and function of Na⁺/Ca²⁺ exchangers 1 and 3 in human macrophages and monocytes

et al. 2009

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The Na 1 /Ca 21 exchanger (NCX) is a membrane transporter that can switch Na 1 and Ca 21 in either direction to maintain the homeostasis of intracellular Ca 21 . Three isoforms (NCX1, NCX2, and NCX3) have been characterized in excitable cells, e.g. neurons and muscle cells. We examined the expression of these NCX isoforms in primary human lung macrophages (HLM) and blood monocytes. NCX1 and NCX3, but not NCX2, are expressed in HLM and monocytes at both mRNA and protein levels. Na 1 -free medium induced a significant increase in intracellular calcium concentration ([Ca 21 ] i ) in both cell types. This response was completely abolished by the NCX inhibitor 5-(N-4-chlorobenzyl)-20,40-dimethylbenzamil (CB-DMB). Moreover, inhibition of NCX activity during Ca 21 -signaling induced by histamine caused a delay in restoring baseline [Ca 21 ] i . Na 1 -free medium induced TNF-a expression and release in HLM comparable to that caused by LPS. TNF-a release induced by Na 1 -free medium was blocked by CB-DMB and greatly reduced by RNAi-mediated knockdown of NCX1. These results indicate that human macrophages and monocytes express NCX1 and NCX3 that operate in a bidirectional manner to restore [Ca 21 ] i , to generate Ca 21 -signals, and to induce TNF-a production. Therefore, NCX may contribute to regulate Ca 21 homeostasis and proinflammatory functions in human macrophages and monocytes.Key words: Ca 21 -signaling . Macrophages . Monocytes . Na 1 /Ca 21 exchanger IntroductionThe Na 1 /Ca 21 exchanger (NCX) is a plasma membrane protein involved in the homeostasis of intracellular Ca 21 [1]. NCX is a bidirectional ion transporter that catalyzes the exchange of Na 1 and Ca 21 depending on their electrochemical gradients [2]. Under physiological conditions, NCX's primary role is to extrude Ca 21 from cells using the Na 1 gradient across the cell membrane (forward mode of operation) [3]. However, in some cases it can contribute to the Ca 21 influx into the cells by working in the reverse mode (i.e. coupling Ca 21 influx with Na 1 efflux) [4][5][6].Three isoforms of NCX, NCX1, NCX2, and NCX3 have been cloned in mammals, outlining a multigene family whose members share a similar molecular structure [7]. NCX is modeled with nine transmembrane segments involved in ion transport and a long central cytoplasmic loop that has regulatory functions [8]. However, truncated forms lacking certain transmembrane segments, but still possessing NCX activity, have also been Eur. J. Immunol. 2009. 39: 1405-1418 DOI 10.1002 Leukocyte signaling 1405 described as the result of alternative splicing of the three genes [9][10][11]. NCX1 is largely predominant in mammalian tissues such as heart, brain, and kidney while the expression of NCX2 and NCX3 appears to be limited to the brain and skeletal muscle [7]. NCX is a key element regulating intracellular Ca 21 concentrations ([Ca 21 ] i ) in many excitable cells, including myocardiocytes, retinal rod photoreceptors, smooth muscle cells, and neurons [3]. Non-excitable cells such as renal epithelial ce...

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“…The stimulation of phospholipase C-b catalyses the hydrolysis of phosphatidylinositol 4,5-bisphosphate generating inositol-1,4,5-trisphosphate and diacylglycerol (Rebecchi & Pentyala, 2000). Inositol-1,4,5-trisphosphate triggers the release of calcium from intracellular stores, whereas diacylglycerol activates speci®c isoforms of protein kinase C. Downstream signalling events attributed to histamine H 1 receptor-mediated increases in intracellular calcium include the modulation of calcium/ calmodulin-dependent enzymes such as nitric oxide synthetase, phospholiapse A 2 and adenylyl cyclase (Leurs et al, 1995). In contrast, protein kinase C is known to be involved in histamine H 1 receptor stimulation of the p42/p44 mitogenactivated protein kinase (MAPK) pathway in DDT 1 MF-2 cells and activation of the c-fos promoter in transfected CHO cells (Megson et al, 2001;Robinson & Dickenson, 2001).…”

Section: Introductionmentioning

confidence: 99%

Stimulation of protein kinase B and p70 S6 kinase by the histamine H₁ receptor in DDT₁MF‐2 smooth muscle cells

Dickenson

2002

British J Pharmacology

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1 Previous studies have shown that the histamine H 1 receptor activates p42/p44 mitogen-activated protein kinases (MAPK) in DDT 1 MF-2 smooth muscle cells via a phosphatidylinositol 3-kinase (PI-3K)-dependent pathway. In this study the e ect of histamine H 1 receptor stimulation on protein kinase B (PKB) and p70 S6 kinase, both of which are downstream targets of PI-3K, has been investigated. Increases in PKB and p70 S6 kinase activation were monitored by Western blotting using phospho-speci®c PKB (Ser 473 ) and p70 S6 kinase (Thr 421 /Ser 424 ) antibodies. 2 Histamine stimulated time and concentration-dependent increases in the phosphorylation of PKB and p70 S6 kinase in DDT 1 MF-2 cells. Both responses were completely inhibited by the histamine H 1 receptor antagonist mepyramine and following pre-treatment with pertussis toxin, to block G i /G o protein dependent pathways. 3 The PI-3K inhibitors wortmannin (IC 50 5.9+0.5 nM) and LY 294002 (IC 50 6.9+0.8 mM) attenuated the increase in PKB phosphorylation induced by histamine (100 mM) in a concentration-dependent manner. 4 Histamine-induced increases in p70 S6 kinase phosphorylation were partially sensitive to rapamycin (20 nM; 68% inhibition) but completely blocked by wortmannin (100 nM), LY 294002 (30 mM) and the MAPK kinase inhibitor PD 98059 (50 mM). 5 In summary, these data demonstrate that the histamine H 1 receptor stimulates PKB and p70 S6 kinase phosphorylation in DDT 1 MF-2 smooth muscle cells. However, functional studies revealed that histamine does not stimulate DDT 1 MF-2 cell proliferation or attenuate staurosporine-induced caspase-3 activity. The challenge for future research will be to link the stimulation of these kinase pathways with the physiological and pathophysiological roles of the histamine H 1 receptor.

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Molecular pharmacological aspects of histamine receptors

Cited by 332 publications

References 275 publications

Histamine H3 Receptor Antagonists Potentiate Methamphetamine Self-Administration and Methamphetamine-Induced Accumbal Dopamine Release

Histamine H3 Receptor Antagonists Potentiate Methamphetamine Self-Administration and Methamphetamine-Induced Accumbal Dopamine Release

Expression and function of Na⁺/Ca²⁺ exchangers 1 and 3 in human macrophages and monocytes

Stimulation of protein kinase B and p70 S6 kinase by the histamine H₁ receptor in DDT₁MF‐2 smooth muscle cells

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Molecular pharmacological aspects of histamine receptors

Cited by 332 publications

References 275 publications

Histamine H3 Receptor Antagonists Potentiate Methamphetamine Self-Administration and Methamphetamine-Induced Accumbal Dopamine Release

Histamine H3 Receptor Antagonists Potentiate Methamphetamine Self-Administration and Methamphetamine-Induced Accumbal Dopamine Release

Expression and function of Na+/Ca2+ exchangers 1 and 3 in human macrophages and monocytes

Stimulation of protein kinase B and p70 S6 kinase by the histamine H1 receptor in DDT1MF‐2 smooth muscle cells

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Expression and function of Na⁺/Ca²⁺ exchangers 1 and 3 in human macrophages and monocytes

Stimulation of protein kinase B and p70 S6 kinase by the histamine H₁ receptor in DDT₁MF‐2 smooth muscle cells